Function of the TCR alpha enhancer in alphabeta and gammadelta T cells

Immunity. 1997 Oct;7(4):505-15. doi: 10.1016/s1074-7613(00)80372-6.

Abstract

We have used gene targeted mutational approaches to assess the role of the T cell receptor alpha (TCR alpha) enhancer (E alpha) in the control of TCR alpha and TCR delta gene rearrangement and expression. We show that E alpha functions in cis to promote V alpha to J alpha rearrangement across the entire J alpha locus, a distance of greater than 70 kb. We also show that E alpha is required for normal alphabeta T cell development; in this lineage, E alpha is required for germline J alpha expression, for normal expression levels of rearranged V alpha J alpha genes, and for expression of a diverse V alpha repertoire. In gamma delta T cells, E alpha is not required for VdeltaDJdelta rearrangement, but, surprisingly, is required for normal expression levels of mature VdeltaDJdelta transcripts and for expression of germline J alpha transcripts. Our findings imply that E alpha function is not limited to the TCR alpha components of the TCRalpha/delta locus or to the alpha beta lineage; rather, E alpha function is important in both alphabeta and gammadelta lineage T cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor*
  • Genes, T-Cell Receptor alpha / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Sequence Deletion
  • T-Lymphocytes / physiology*
  • Thymus Gland / cytology*
  • Transcription, Genetic

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta